CONTINUOUS CONTRACTILE ACTIVITY INDUCES FIBER-TYPE SPECIFIC EXPRESSION OF HSP70 IN SKELETAL-MUSCLE

Continuous contractile activity of skeletal muscle elicits an early an d dramatic increase in ribosomal RNA, suggesting that translational ef ficiency and/or capacity is enhanced during the adaptive response to i ncreased metabolic demand. In view of the important role heat shock or stress proteins (HSPs) play as molecular chaperones during protein sy nthesis, we examined whether expression of the inducible 70-kDa HSP (H SP70) and/or mitochondrial 60-kDa HSP (HSP60) is altered in rabbit tib ialis anterior muscle during continuous low-frequency motor nerve stim ulation. Induction of the HSP70 gene was evident within 24 h after the onset of stimulation as reflected by increases in HSP70 transcription ( >20-fold) and mRNA(>50-fold). HSP70 protein levels were significantl y elevated (10- to 12-fold) after 14 and 21 days of stimulation. Mitoc hondrial HSP60 mRNA and protein also increased during stimulation (>18 - and >5-fold after 21 days, respectively). In situ hybridization and immunohistochemistry coupled with myosin ATPase staining revealed that expression of HSP70 was restricted to oxidative type I and IIa fibers during the first 3 days of stimulation but shifted to primarily type II fibers after 21 days of stimulation. These findings demonstrate tha t induction of HSP70 during the adaptive response to chronic motor ner ve stimulation proceeds from type I/IIa to type IId(x)/b fibers, sugge sting that the expression of HSPs may be required to support the foldi ng and compartmentalization of nascent proteins during the transformat ion process.